This is a continuation of an on-going research project (DA 01207) concerns with the interaction of drugs of abuse with neuroregulators (compounds which may act as neurotransmitters or neuromodulators), with an emphasis upon regulatory mechanisms in a programatic series of investigations. Included among the drugs of abuse under investigation are cocaine, amphetamine, and morphine. There are four prongs to the research effort. The first examines the effect of stimulant drugs upon catecholamine synthesis. We have found that cocaine and amphetamine have differential effects upon synaptosomal mechanisms and would examine these processes both in vitro and in vivo. Included in this section are studies utilizing soluble tyrosine hydroxylase. The second prong examines the effects of acute and chronic administration of various drugs of abuse on the in vivo release of biogenic amines, utilizing a continuous perfusion of the ventricular system of the brain with assays by mass fragmentographic techniques (GC-MS). Using these systems, we can also examine release of opiod-peptides. The third prong looks at behavioral concomitants of administration of drugs of abuse, with particular attention to the effects of amphetamine and cocaine on social behavior in rhesus. In the fourth research area, we examine directly the effects of opiates on the concentrations and turnover of various opioid peptides, including enkephalins and endorphins, utilizing highly specific antibodies and assays, several of which have been developed in our laboratory. Through these interrelated studies we would hope to learn more about the mechanisms of action of these drugs with the goal of more effective treatment and prevention of drug abuse.